Immunopathology resulting from lack of early control of influenza virus infection by interferon-induced Mx proteins: causes and consequences (C01)

• Subject Area: Virology
• Term: since 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 256073931

This project will follow the observation that rare variants of the human restriction factor MxA increase the risk to contract zoonotic influenza A viruses (IAVs). C01 will continue to study genetic and immunological susceptibility factors for avian IAV infections by reanalyzing the genomic data of H7N9-infected patients and healthy controls from the second funding period to identify additional, rare genetic defects affecting H7N9 susceptibility and by investigating whether anti-interferon autoantibodies predispose humans to H7N9 infections. C01 will also examine the MxA interactome. Identified risk factors will be further characterized in an IAV infection model in human lung organoids. Moreover, they will investigate the role of the dominant-negative effect of inactive MxA variants on wild-type MxA in the emergence of IAV variants able to escape MxA restriction in a heterozygous, MxA transgenic mouse model.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1160: Immune-mediated pathology as a consequence of impaired immune reactions (IMPATH)
• Applicant Institution: Albert-Ludwigs-Universität Freiburg
• Project Heads: Dr. Laura Graf; Professor Dr. Martin Schwemmle